Prenatal vitamin D supplementation mitigates inflammation-related alveolar remodeling in neonatal mice

Abstract

The development of chronic lung disease in the neonate, also known as bronchopulmonary dysplasia (BPD), is the most common long-term complication in prematurely born infants. In BPD, the disease-characteristic inflammatory response culminates in nonreversible remodeling of the developing gas exchange area, provoked by the impact of postnatal treatments such as mechanical ventilation (MV) and oxygen treatment. To evaluate the potential of prenatal treatment regimens to modulate this inflammatory response and thereby impact the vulnerability of the lung towards postnatal injury, we designed a multilayered preclinical mouse model. After administration of either prenatal vitamin D enriched (VitD+; 1,500 IU/g food) or deprived (VitD-; <10 IU/Kg) food during gestation in C57B6 mice (the onset of mating until birth), neonatal mice were exposed to hyperoxia (FiO2=0.4) with or without MV for 8h at day 5-7 of life, whereas controls spontaneously breathed room air. Prenatal vitamin D supplementation resulted in a decreased number of monocytes/macrophages in the neonatal lung undergoing postnatal injury together with reduced TGF-β pathway activation. In consequence, neonatal mice that received a VitD+ diet during gestation demonstrated less ECM remodeling upon lung injury, reflected by the reduction of pulmonary α-smooth muscle actin-positive fibroblasts, decreased collagen and elastin deposition, and lower amounts of interstitial tissue in the lung periphery. In conclusion, our findings support strategies that attempt to prevent vitamin D insufficiency during pregnancy as they could impact lung health in the offspring by mitigating inflammatory changes in neonatal lung injury and ameliorating subsequent. remodeling of the developing gas exchange area.

The Association of Vitamin D during Pregnancy and mRNA Expression Levels of Inflammatory Factors with Preterm Birth and Prelabor Rupture of Membranes

“…VD has anti-inflammatory effects and can regulate a variety of immune cells (such as monocytes, macrophages, B cells, and T cells) to reduce the production of pro-inflammatory factors and increase the level of anti-inflammatory factors [17]. Experiments in mice have shown that prenatal vitamin D supplementation leads to a decrease in the number of macrophages in the lungs of newborns [18]. Cell experiments showed that mRNA expression levels of IL-1β were reduced in 1,25(OH) 2 D 3 -treated uterine myocytes [19].…”